This proposal will study the biological properties of the medial entorhinal cortical-hippocampal network that enable it to perform spatial processing functions. This research will focus on biological mechanisms of grid cell formation and theta phase precession. Grid cells are spatially sensitive cells in medial entorhinal cortex that fire whenever an animal is positioned in the firing fields of the cell, in a hexagonal array of position in the environment. Interactions between grid cells in entorhinal cortex and place cells in the hippocampus are thought to be important in overall spatial functions, such as coding the position of the animal and planning future paths. Theta phase precession is a phenomenon that occurs in place cells (spatially sensitive cells that fire whenever an animal is in a certain locaton of an environment). Place cells shift their phase of firing relative to network theta rhythm oscillations in a manner suggesting that populations of cells organize their activity to allow for compressed neural activity representing a trajectory. This representation could be useful for encoding of trajectories in memory and planning of future trajectories. This research will use a large scale, biologically constrained model of the medial entorhinal cortical- hippocampal network to assess the ability of a biologically realistic network to support the various models of grid cell formation and theta phase precession that have been previously proposed. The knowledge gained from this work will allow a broader understanding of the mechanisms by which various neurological disorders such as epilepsy and Alzheimer's disease can adversely affect cognitive functions such as spatial processing and memory. Further, the computational model produced by this work will be freely shared and can be used to search for and quantify potential therapeutic targets for various disorders.